ABSTRACT
Silicosis is an occupational pulmonary fibrosis caused by inhalation of silica (SiO2) and there are no ideal drugs to treat this disease. Earthworm extract (EE), a natural nutrient, has been reported to have anti-inflammatory, antioxidant, and anti-apoptosis effects. The purpose of the current study was to test the protective effects of EE against SiO2-induced pulmonary fibrosis and to explore the underlying mechanisms using both in vivo and in vitro models. We found that treatment with EE significantly reduced lung inflammation and fibrosis and improved lung structure and function in SiO2-instilled mice. Further mechanistic investigations revealed that EE administration markedly inhibited SiO2-induced oxidative stress, mitochondrial apoptotic pathway, and epithelial-mesenchymal transition in HBE and A549 cells. Furthermore, we demonstrate that Nrf2 activation partly mediates the interventional effects of EE against SiO2-induced pulmonary fibrosis. Our study has identified EE to be a potential anti-oxidative, anti-inflammatory, and anti-fibrotic drug for silicosis.
Subject(s)
Antioxidants/therapeutic use , Disease Models, Animal , Lung/drug effects , Materia Medica/therapeutic use , Oligochaeta/chemistry , Pulmonary Fibrosis/prevention & control , Silicosis/drug therapy , Tissue Extracts/therapeutic use , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antioxidants/administration & dosage , Antioxidants/pharmacology , Apoptosis/drug effects , Cell Line , Cells, Cultured , Epithelial-Mesenchymal Transition/drug effects , Injections, Intraperitoneal , Lung/metabolism , Lung/pathology , Lung/physiopathology , Male , Materia Medica/administration & dosage , Materia Medica/pharmacology , Mice, Inbred C57BL , NF-E2-Related Factor 2/agonists , NF-E2-Related Factor 2/antagonists & inhibitors , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Oxidative Stress/drug effects , Pulmonary Fibrosis/etiology , Pulmonary Fibrosis/immunology , RNA Interference , Random Allocation , Respiratory Mucosa/cytology , Respiratory Mucosa/drug effects , Respiratory Mucosa/metabolism , Respiratory Mucosa/pathology , Silicosis/metabolism , Silicosis/pathology , Silicosis/physiopathology , Specific Pathogen-Free Organisms , Tissue Extracts/administration & dosage , Tissue Extracts/pharmacologyABSTRACT
Kochiae Fructus (KF) was listed as 'top grade' medicinal material by the 'Shennong's Herbal Classic of Materia Medica' and has been used in traditional Chinese medicine to delay aging and treat inflammation, such as rubella, eczema, cutaneous pruritus, etc. Our research focused on the antioxidant capability of water decoction and fractions from KF based on 2,2-iphenyl-1-picrylhydrazyl (DPPH) free radical and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) cation radical scavenging assay, the ferric reducing antioxidant power assay, and inhibitory effects on DNA and protein oxidative damage. The results of total phenolics and flavonoids contents showed that ethyl acetate fraction (EAF) possessed the highest phenolics and flavonoids with values of 112.90 ± 9.58 mg gallic acid equivalents/g and 329.60 ± 20.93 mg rutin equivalents/g, respectively. At the same time, the results of antioxidant capacities showed that EAF possessed best antioxidant abilities. In addition, in this work, we evaluated the oral safety of the water decoction of KF (KFWD) via the 14-day acute and 28-day subacute toxicity tests. The results of in vivo toxicity assessment showed that KFWD did not cause significant changes in the general clinical symptoms, hematology and biochemical parameters, organ weights, or histopathological appearances in mice or rats. In summary, the reason why KF has the traditional effect on delaying aging may be related to the fact that its rich in flavonoids and phenolics. Simultaneously, no toxicity was detected after acute or subacute treatment of KFWD, providing valuable evidence for the traditional safe use of KF.